Colostrum is a component of the milk of mammals during the first few days after birth. Colostrum is a thick yellowish fluid and is the first lacteal secretion post parturition and contains a high concentration of immunogloblins (IgG, IgM, and IgA) and a variety of non-specific proteins. Colostrum also contains various cells such as granular and stromal cells, neutrophils, monocyte/macrophages, and lymphocytes. Colostrum also includes growth factors, hormones, and cytokines. Unlike mature breast milk, colostrum contains low sugar, low iron, but is rich is lipids, proteins, mineral salts, vitamins, and immunoglobins.
Colostrum also includes or contains a proline-rich polypeptide aggregate or complex, which is referred to as colostrinin. One peptide fragment of colostrinin is Val-Glu-Ser-Tyr-Val-Pro-Leu-Phe-Pro (SEQ ID NO:31), which is disclosed in International Publication No. WO-A-98/14473. Colostrinin and this fragment have been identified as useful in the treatment of disorders of the central nervous system, neurological disorders, mental disorders, dementia, neurodegenerative diseases, Alzheimer""s disease, motor neurone disease, psychosis, neurosis, chronic disorders of the immune system, diseases with a bacterial and viral aetiology, and acquired immunological deficiencies, as set forth in International Publication No. WO-A-98/14473.
Although certain uses for colostrinin have been identified, it would represent an advancement in the art to discover and disclose other uses for colostrinin or a component thereof, that are not readily ascertainable from the information currently known about colostrinin or its constituents.
The present invention relates to the use of colostrinin, at least one constituent (i.e., component) peptide thereof, at least one active analog thereof (e.g., peptide having an N-terminal sequence equivalent to an N-terminal sequence of at least one of the colostrinin constituent peptides), and combinations thereof, as an oxidative stress regulator. These oxidative stress regulators can be used in vitro or in vivo, including internal and external use in animals including mammals such as humans. They can be used for preventative (i.e., prophylactic) treatments or for therapeutic treatments.
In one embodiment, the present invention provides a method for modulating (e.g., regulating or adjusting) the oxidative stress level in a cell. The method includes contacting the cell with an oxidative stress regulator selected from the group of colostrinin, a constituent peptide thereof, an active analog thereof, and combinations thereof, under conditions effective to change (decrease or increase, but preferably, decrease) or prevent an increase in the level of an oxidizing species in the cell. By this it is meant that no increase or any amount of change (preferably, a decrease) in the level of one or more oxidizing species are within the scope of the invention, although not all oxidizing species monitored would necessarily have to demonstrate a change (preferably, decrease) or lack of an increase in its level. The cell can be in a cell culture, a tissue, an organ, or an organism. Hence, this method can be carried out in vivo or in vitro.
In another embodiment, the present invention provides a method for modulating the oxidative stress level in a patient. The method includes administering to the patient an oxidative stress regulator selected from the group of colostrinin, a constituent peptide thereof, an active analog thereof, and combinations thereof, under conditions effective to decrease or prevent an increase in the level of an oxidizing species in the patient. By this it is meant that no increase or any amount of change (increase or decrease, but preferably, a decrease) in the level of one or more oxidizing species are within the scope of the invention, although not all oxidizing species monitored would necessarily have to demonstrate a decrease or lack of an increase in its level.
Yet another method of the invention is a method of modulating the oxidative stress level of the skin of a patient, and preferably, treating (prophylactically or therapeutically) oxidative damage to the skin of a patient. The method includes applying to skin a topical formulation (e.g., sun screen) that includes an oxidative stress regulator selected from the group of colostrinin, a constituent peptide thereof, an active analog thereof, and combinations thereof, under conditions effective to change (increase or decrease, but preferably, decrease) or prevent an increase in the level of damage to a biomolecule of the patient. By this it is meant that no increase or any amount of change (increase or decrease, but preferably, decrease) in the level or damage to one or more biomolecules are within the scope of the invention, although not all biomolecules monitored would necessarily have to demonstrate a decrease or lack of an increase in its level of damage. The biomolecule may be selected from the group of a DNA, a protein, a lipid, or combinations thereof.
In other embodiments, the invention provides the use of an oxidative stress regulator in the manufacture of a medicament for use in the methods described herein.
A further embodiment of the invention is a cosmetic formulation that includes an oxidative stress regulator selected from the group of colostrinin, a constituent peptide thereof, an active analog thereof, and combinations thereof.
As used herein, xe2x80x9caxe2x80x9d or xe2x80x9canxe2x80x9d means one or more (or at least one), such that combinations of active agents (i.e., active oxidative stress regulators), for example, can be used in the compositions and methods of the invention. Thus, a composition that includes xe2x80x9caxe2x80x9d polypeptide refers to a composition that includes one or more polypeptides.
xe2x80x9cAmino acidxe2x80x9d is used herein to refer to a chemical compound with the general formula: NH2xe2x80x94CRHxe2x80x94COOH, where R, the side chain, is H or an organic group. Where R is organic, R can vary and is either polar or nonpolar (i.e., hydrophobic). The amino acids of this invention can be naturally occurring or synthetic (often referred to as nonproteinogenic). As used herein, an organic group is a hydrocarbon group that is classified as an aliphatic group, a cyclic group or combination of aliphatic and cyclic groups. The term xe2x80x9caliphatic groupxe2x80x9d means a saturated or unsaturated linear or branched hydrocarbon group. This term is used to encompass alkyl, alkenyl, and alkynyl groups, for example. The term xe2x80x9ccyclic groupxe2x80x9d means a closed ring hydrocarbon group that is classified as an alicyclic group, aromatic group, or heterocyclic group. The term xe2x80x9calicyclic groupxe2x80x9d means a cyclic hydrocarbon group having properties resembling those of aliphatic groups. The term xe2x80x9caromatic groupxe2x80x9d refers to mono- or polycyclic aromatic hydrocarbon groups. As used herein, an organic group can be substituted or unsubstituted.
The terms xe2x80x9cpolypeptidexe2x80x9d and xe2x80x9cpeptidexe2x80x9d are used interchangeably herein to refer to a polymer of amino acids. These terms do not connote a specific length of a polymer of amino acids. Thus, for example, the terms oligopeptide, protein, and enzyme are included within the definition of polypeptide or peptide, whether produced using recombinant techniques, chemical or enzymatic synthesis, or naturally occurring. This term also includes polypeptides that have been modified or derivatized, such as by glycosylation, acetylation, phosphorylation, and the like.
The following abbreviations are used throughout the application: